tbuckley/cabot-search huggingface dataset:
IFCT-2105 lurbiclin real-world effectiveness and treatment sequences in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) who received lurbinectedin as part of the French Early Access Program (EAP-ATU).
Authors: Nicolas Girard, Florian Guisier, Aurélie Swalduz, Sylvie Van Hulst, Eric Pichon, Pernelle Lavaud, Laurent Greillier, Angelica Tiotiu, Anne Madroszyk, Olivier Bylicki, Anthony Canellas, Laure Belmont, Maeva Zysman, Pierre-Alexandre Hauss, Benoit Godbert, Clarisse Audigier-Valette, Cléa Lebreton, Franck Morin, Virginie Westeel
Journal: Journal of Clinical Oncology (2023)

8584 Background: Novel options are needed for pts with ES-SCLC after the failure of first-line chemotherapy. Lurbinectedin demonstrated efficacy in a landmark phase II study [Trigo et al. Lancet Oncol. 2020 May;21(5):645], and was granted EAP-ATU in France in June 2020. Methods: Multicenter, retrospective cohort of consecutive pts with histologically or cytologically confirmed ES-SCLC, who received at least one dose of treatment with lurbinectedin as part of the French EAP-ATU from June 2020 until March 2021, and gave consent for the data collection, were enrolled in 47 sites. Primary and secondary endpoints were description of clinical characteristics, and exposure to treatment, response, PFS, OS, safety. Results: 312 pts – 64% male, median age 65 years, 72% PS0-1, 47% with brain metastasis, 58% with previous immunotherapy – were enrolled. Lurbinectedin was administered as second-line in 44% of pts; 58% were chemotherapy-refractory. Pts received a median number of 3 cycles of lurbinectedin. Concurrent radiotherapy on metastases was delivered to 38% of pts. Lurbinectedin was discontinued because of progression/death/toxicity/other reasons in 83%/8%/5%/4% of pts. Grade3/4 events were observed in 9%/5% of pts. Response rate was 22% [95%CI 17-27%], disease control rate was 38% [95%CI 32-44%]. After a median follow-up of 20.8 months, median PFS and OS were 1.9 [95%CI 1.8-2] and 4.7 [95%CI 4-5.4] months; 6-month PFS and OS were 7% [4-10%] and 42% [95%CI 37-48%]. PS≤2 and chemotherapy-free interval≥90days were associated with significantly longer OS (HR = 0.71 [95%CI 0.53-0.95] and HR = 0.58 [95% CI 0.44-076] respectively). Main sites of progression were the lung (39% of pts), the brain (39% of pts), the liver (30% of pts), and the mediastinum (30% of pts). Subsequent treatment was administered to 154 pts after discontinuation of lurbinectedin, mostly consisting of topotecan (26% of pts); response/disease control rates, and median PFS of first subsequent treatment were 11% [95%CI 6-17%], 35% [95%CI 27-44%], and 1.9 [95%CI 1.7-2.3] months. Conclusions: Lurbinectedin provides an additional option from second-line for ES-SCLC, with efficacy outcomes comparable to that of historical treatments.
MagnetisMM-6: An open-label, multicenter, randomized phase 3 study of elranatamab + daratumumab + lenalidomide (EDR) versus daratumumab + lenalidomide + dexamethasone (DRd) in transplant ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM).
Authors: Sebastian Grosicki, Su-Peng Yeh, Jeffrey S.Y. Huang, Ja Min Byun, Christine DiRienzo, Andrea Viqueira
Journal: Journal of Clinical Oncology (2023)

TPS8065 Background: Elranatamab, a humanized bispecific antibody targeting B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, has shown promising efficacy and acceptable safety in clinical studies, as monotherapy (MagnetisMM-3, NCT04649359) and in combination with daratumumab (MagnetisMM-5, NCT05020236), in the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Despite recent advances in the treatment of NDMM, MM remains incurable and more effective treatment options are needed. The aim of the MagnetisMM-6 study (NCT05623020) is to evaluate EDR versus DRd for TI patients with NDMM. Methods: MagnetisMM-6 is an ongoing, open-label, 2-arm, multicenter, randomized phase 3 study estimated to enroll ~646 patients. There are 2 parts: Part 1 evaluates the safety and recommended phase 3 dose (RP3D) of EDR: Part 2 evaluates the efficacy and safety of EDR at RP3D vs DRd in TI patients with NDMM. TI is defined as age ≥65 or age &lt; 65 with comorbidities impacting the possibility of transplant. The primary endpoints of Part 2 are minimal residual disease (MRD) at 12 mo and progression-free survival. Secondary endpoints include overall and sustained MRD negativity rates, duration of MRD negativity, objective response rate, complete response (CR) rate, time to response, duration of response, duration of CR, overall survival, safety, quality of life, immunogenicity, and pharmacokinetics. Part 1 includes TI patients with NDMM as well as patients with RRMM who have received 1−2 prior lines of therapy including ≥1 immunomodulatory drug and ≥1 proteasome inhibitor. Part 2 includes only TI patients with NDMM. Key inclusion criteria are: ≥18 y; a diagnosis of MM (according to International Myeloma Working Group [IMWG] criteria); an ECOG performance status ≤2; and measurable disease based on IMWG criteria (serum M-protein ≥0.5 g/dL, urinary M-protein excretion ≥200 mg/24 hr, or involved serum free light chain [FLC] ≥100 mg/L and abnormal serum immunoglobulin κ:λ FLC ratio [ &lt; 0.26 or &gt; 1.65]). Key exclusion criteria are: smoldering MM; monoclonal gammopathy; Waldenström’s macroglobulinemia; plasma cell leukemia; active, uncontrolled bacterial, fungal, or viral infections; previous systemic treatment for MM (NDMM patients only); previous treatment with a BMCA-directed therapy or anti-CD38-directed therapy ≤6 mo of the first dose of study treatment (RRMM patients only); or stem cell transplant ≤3 mo of the first dose of study treatment or active graft versus host disease (RRMM patients only). As of February 2023, the study is open and enrolling at 9 sites in 5 countries. Clinical trial information: NCT05623020 .
Comparing PD-L1 scores for predicting pembrolizumab efficacy in first-line treatment of unresectable cutaneous squamous cell carcinomas.
Authors: Eve Maubec, Marouane Boubaya, Lydia Deschamps, Marie Beylot-Barry, Peter Petrow, Isabelle Scheer-Senyarich, Nicole Basset-Seguin, Jean-Jacques Grob, Brigitte Dreno, Coralie Bloch-Queyrat, Marie Thérèse Leccia, Andreea Raluca Stefan, Philippe Saiag, Florent Grange, Nicolas Meyer, Sophie Dalac, Céline Alloux, Isabelle Lopez, Annick Tibi, Vincent Lévy
Journal: Journal of Clinical Oncology (2023)

e21593 Background: In the CARSKIN study (NCT02883556), 1L pembrolizumab demonstrated promising activity with durable responses and manageable safety in patients (pts) with unresectable locally advanced or metastatic CSCC. Here we report best ORR and survival endpoints of the entire cohort by PD-L1 status. Methods: The imaging assessment per RECIST v1.1 was blinded with independent central review. Best ORR, PFS, DOR OS, in the overall sample and by PD-L1 status was centrally assessed by 2 blinded independent pathologists, one using the anti–PD-L1 E1L3N clone (TPS E1L3N ), the other using the 22C3 antibody (TPS 22C3 and CPS 22C3 ). Among 57 pts, 6 were excluded from the analysis: 2 untreated pts, 1 early unrelated death and 3 pts tested only with 1 assay). ROC curve analysis was used to compare assays. Results: With a median follow-up of 26 mo, best ORR was 51% with 14 PR (27%) and 12 CR (24%). Relapse occurred in 3 PR and 1 PD-L1 – CR pts. Respective median PFS, DOR, and OS were 13.7, NR, and 25.3 mo; respective 1-year PFS, DOR and OS were 50% [38-66], 80% [65-97] and 73% [61-86]. With a cutoff of 1%, best ORR was higher either for TPS E1L3N + pts vs TPS E1L3N – pts (60% vs 18%, p = 0.02) and for CPS 22C3 + pts (59% vs 20%, p = 0.038), but not TPS 22C3 + pts (p = 0.76). The optimal cutoff of CPS 22C3 for ORR using a ROC curve was estimated to be ≥ 7% with a sensitivity of 0.70 and a specificity of 0.75. For best ORR, area under the ROC curve was higher for CPS 22C3 (0.72) than TPS E1L3N (0.62) but the difference was not significant (P = 0.21). Pts with TPS E1L3N ≥ 1% had a higher 1-y PFS (57% vs 27%, p = 0.004) and OS (82% vs 42%, P = 0.01). Pts with CPS 22C3 ≥ 1%, had a better 1-y OS (79% vs 50%, p = 0.03), but not 1y-PFS. Conclusions: CPS 22C3 ≥ 7% appeared equivalent to TPS E1L3N ≥ 1% for predicting ORR and OS in pts receiving pembrolizumab in 1L treatment of advanced or metastatic CSCCs. Replications are warranted for validation. Pts with low scores might beneficiate from combined treatments. Clinical trial information: NCT02883556 .
First-in-human, multicenter phase Ⅰ study of TGRX-326 in patients with advanced ALK-positive non-small cell lung cancer.
Authors: Hongyun Zhao, Yuxiang Ma, Nong Yang, Zhehai Wang, Wenjian Jin, Xingya Li, Yunpeng Liu, Rui Meng, Jianying Zhou, Ying Cheng, Yongsheng Wang, Zhuang Yu, Li Zhang
Journal: Journal of Clinical Oncology (2023)

9113 Background: TGRX-326, a deuterated derivative of lorlatinib (LOR), is a potent 3 rd generation ALK and ROS1 dual TKI with high potency against multiple ALK-resistant mutations. Deuteration of the key metabolic site of the molecule allows to achieve a higher exposure than with LOR and this may result in alleviated toxicities and better efficacy. Methods: The study comprised 3 phases: dose escalation (D-ESCAL), dose expansion (D-EXP) and cohort expansion (C-EXP). In D-ESCAL and D-EXP, ALK+ pts prior failed on 2 nd gen ALK-TKIs or ROS1+ pts resistant to crizotinib (CRZ) were enrolled; in C-EXP, ALK+ pts progression after CRZ (C-EXP-A1),progression after ≥1 2 nd gen TKIs (C-EXP A2), ROS1+ progression after CRZ (C-EXP-B) and pts with ALK TKI naïve (C-EXP-C) were enrolled. Results: Up to Jan 13, 2023, 185 pts (median age 53 years, 45.9% male) were enrolled; Median treatment and follow-up was 5.5 and 6.7 months, respectively. There were no DLT observed and no MTD identified in D-ESCAL (5-125mg QD, n=19). Based on the safety, efficacy and PK exposure data of 42 pts in D-ESCAL and D-EXP, 60 mg QD was selected as the RP2D for C-EXP,the average AUC tau of 60mg QD reached to 5443ng*hr/mL. Treatment-related adverse events (TRAEs) occurred in 87.5% patients (162/185), the most common TRAEs were hypercholesterolemia (74.1%), hypertriglyceridemia (68.1%), weight gain (36.2%), peripheral edema (15.7%), peripheral neuropathy (14.1%). As for R2PD, 132 of 155 (85.2%) experienced TRAEs, Grade ≥3 TRAEs occurred in 19.7%, most frequent were hypertriglyceridemia (11%) and hypercholesterolemia (8.4% ). Dose interruptions and dose reductions associated with TRAEs were reported in 10 (5.4%) and 5 (2.7%) pts respectively. Confirmed response were observed in 142 ALK+pts enrolled in C-EXP, results are shown in the Table (Efficacy of B-ROS1+ pts will be reported separately). Eleven ALK mutations were detected in 16 pts (either alone or in combination); 50.0% pts achieved PR. Out of 6 pts who were positive for G1202R, 50.0% experienced PR. Conclusions: TGRX-326 was well tolerated in pts with advanced ALK+ NSCLC and showed promising clinical antitumor activity irrespectively of ALK+ resistance to CRZ and 2 nd gen TKIs, especially among those with brain metastases. Impressive activity was seen in ALK TKI naïve NSCLC. TGRX-326 demonstrated antitumor activity against multiple ALK mutations including G1202R. Clinical trial information: NCT05441956 . [Table: see text]
Risk and protective factors for dementia in cancer survivors vary by cancer type.
Authors: Bryan Neth, Jonathan Graff-Radford, Eva Alden, Hugo Botha, Aditya Raghunathan, Derek R. Johnson, Daniel Honore Lachance, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri, James Robert Cerhan, David S. Knopman
Journal: Journal of Clinical Oncology (2023)

e24089 Background: Little is known about risk and protective factors for dementia in cancer survivors. With increasing longevity due to improved cancer therapy, it’s prudent to study factors contributing to cognitive impairment in this patient population. Methods: We performed multivariable cox regression analyses to assess established risk factors for all-cause dementia (age, education, APOE4-status, social and physical activity engagement) in breast and prostate cancer survivors. Patients 50+ years old with pathology-confirmed cancer diagnosis at Mayo Clinic were identified from a longitudinal, population-based cohort – Mayo Clinic Study of Aging. Analyses were controlled for age, APOE4-status, education, and cancer treatment. Results: We included a total of 209 patients with breast cancer (mean age 75.4 years, 24% APOE4-positive, median follow-up 6.8 years) and 352 with prostate cancer (mean age 77 years, 26% APOE4-positive, median follow-up 6.4 years). 31 patients with breast cancer (15%) and 66 patients with prostate cancer (20%) were diagnosed with dementia at last follow-up. Older age was associated with increased risk for dementia (5-year increase – breast: hazard ratio (HR) 1.9 [95%CI 1.3-2.7, p = 0.001]; prostate: HR 2.4 [95%CI 1.8-3.2, p &lt; 0.0001]). APOE4-positivity was associated with increased dementia risk in breast (HR 3.6 [95%CI 1.6-7.8, p &lt; 0.002]), but not prostate cancer (HR 1.2 [95%CI 0.7-2.0, p = 0.5]). More education was associated with lower dementia risk in prostate cancer (education year: HR 0.91 [95%CI 0.84-0.98, p &lt; 0.02]; education years &gt; 12: HR 0.26 [95%CI 0.1-0.6, p &lt; 0.001]). Physical activity engagement in mid-life was associated with lower dementia risk (prostate: HR 0.56 [95%CI 0.4-0.8, p &lt; 0.005]; breast: HR 0.48 [95%CI 0.3-0.9, p &lt; 0.02]). Conclusions: In this longitudinal, population-based study we found that some risk and protective factors for dementia in cancer survivors vary by cancer type. While advanced age is an expected dementia risk factor, there were mixed results for APOE4-positivity (increased risk only in breast cancer) and education (only protective in prostate cancer). Our results support further study into factors influencing dementia risk by cancer type in hopes of identifying preventative strategies.
Clinical factors associated with prescribing patterns of bone modifying agents in men with metastatic castration-resistant prostate cancer.
Authors: Christopher Kobe, Charles B. Nguyen, Kyle E. Kumbier, Jordan Bauman, Jennifer A. Burns, Phoebe A. Tsao, Jordan B. Sparks, Megan Veresh Caram
Journal: Journal of Clinical Oncology (2023)

e18878 Background: Bone metastases occur in up to 90% of men with metastatic prostate cancer and cause skeletal-related events (SREs) such as fracture and spinal cord compression. Although bone modifying agents (BMAs) have been shown to decrease the risk of SREs in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are not widely used in this patient population. In this retrospective study, we report the prescribing patterns of BMAs and predictors of BMA use in a large national cohort. Methods: We used the VA corporate data warehouse to identify patients with mCRPC who were treated with first-line mCRPC therapy (abiraterone, enzalutamide, docetaxel, or ketoconazole) between 2010 and 2017. BMA prescribing frequency and patterns were analyzed. Multivariable regression analysis was used to evaluate clinical and disease-specific factors associated with BMA use which are presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). Results: In the final cohort of 4,079 patients, the median age at mCRPC diagnosis was 73 years (IQR 66-81). 29% of patients in the cohort were Black. Diagnosis codes identified bone metastases at mCRPC diagnosis in 48% of the cohort (ICD-9 and 10 coding for sites of metastases are known to underestimate the actual incidence of metastases). Only 48% of patients received a BMA following initiation of treatment for mCRPC, 47% of which had already received a BMA 6 months prior to mCRPC diagnosis. For those who were new BMA starts, the median time to BMA administration from mCRPC treatment was 3.4 months (IQR 1.2-8.8). Factors associated with BMA use were having an ICD-9 or 10 diagnosis code for bone metastases at time of mCRPC treatment (OR 1.28, 95% CI 1.10-1.48), concurrent corticosteroid use (OR 1.90, 95% CI 1.53-2.38), and docetaxel use as first-line mCRPC therapy (OR 1.78, 95% CI 1.45-2.18). Factors associated with decreased BMA use were Charlson comorbidity index score of ≥ 2 (OR 0.75, 95% CI 0.62-0.90), advancing age (OR 0.86 per 10 years, 95% CI 0.79-0.94), and decreased eGFR (eGFR 30-59, OR 0.81, 95% CI 0.68-0.96; eGFR 0-29, OR 0.23, 95% CI 0.14-0.37). Having a diagnosis code for a SRE before mCRPC diagnosis (e.g., bone fracture and cord compression) did not impact BMA use, but the incidence of those events was low. Conclusions: Less than half of this VA cohort received a BMA after starting therapy for mCRPC. Key factors associated with BMA use were corticosteroid use and first-line docetaxel use, which likely represented more aggressive disease. Notably, patients who were older and had more comorbid conditions were less likely to receive a BMA despite being highest risk for frailty and SREs. Future quality improvement efforts aimed at increasing BMA use may address the needs of the geriatric mCRPC patient population.
Wireless transcutaneous electric nerve stimulation (TENS) for chemotherapy-induced peripheral neuropathy (CIPN): A proof-of-concept, placebo-controlled, randomized clinical trial (RCT).
Authors: Jennifer S. Gewandter, Eva Culakova, Jenae N Davis, Umang Gada, Joseph John Guido, Brian Leslie Burnette, James D. Bearden, Mark Allen O'Rourke, Karen Michelle Mustian, Gary R. Morrow, Kathleen A Sluka, Nimish Mohile
Journal: Journal of Clinical Oncology (2023)

e24134 Background: Chronic CIPN affects approximately 30%-60% of people who receive neurotoxic chemotherapy. CIPN is associated with impaired quality of life and function and has few effective treatments. Methods: This 6-site, subject and assessor blinded RCT was designed to assess (1) preliminary efficacy (i.e., alpha pre-specified at 0.2) of a wearable, app-controlled, TENS device for chronic CIPN and (2) feasibility of conducting a confirmatory trial within the NCI Community Oncology Research Program (NCORP) (NCT 04367480). The primary outcome was the EORTC-CIPN20. The main secondary outcomes were hot/burning pain, sharp/shooting pain, tingling, numbness, and cramping (7-day daily diary, 0 – 10 numeric rating scales). The TENS device applies stimulation for 1hr treatment sessions followed by 1 hour rest periods. The placebo TENS device is identical, except it delivers only 2.5 mins of stimulation in the treatment period. Subjects were asked to wear the device for 5 hrs/day (i.e., 3 treatment sessions) for 6 weeks. The primary analysis used an ANCOVA with the 6-week EORTC-CIPN20 score as the dependent variable, arm as fixed effect, and baseline EORTC-CIPN20 and site as covariates. Secondary analyses used similar ANCOVA models (excluding site) for each symptom on subgroups of subjects who reported at least 4 out 10 for that symptom at baseline. Results: 142 eligible subjects were randomized and received a device; 130 (91%) completed the study. Subjects were on average 63 years old, 65% female, and 85% white. The most common chemotherapies were taxanes (37%), platinums (36%), or their combination (15%). 88% of study completers received at least 3 treatment sessions on at least 70% of study days. The median time since chemotherapy was 16 months (IQR: 7, 34). See Table for efficacy results. Conclusions: A RCT of an app-controlled, wireless TENS device for chronic CIPN with excellent adherence and retention rates is feasible in NCORP. Preliminary efficacy evidence suggests that TENS is promising for pain and cramping from CIPN, but less likely to improve numbness and tingling. A confirmatory RCT of TENS for painful CIPN is highly warranted. Clinical trial information: NCT04367480 . [Table: see text]
Black voices on gynecologic cancer: Understanding experiences.
Authors: Kimberly Richardson, Onyinye Balogun
Journal: Journal of Clinical Oncology (2023)

e18680 Background: Structural racism and bias affects care of Black gynecologic cancer patients. Factors associated with disparities in Black cancer death rates have been associated with structural racism which has systematically limited the standard of living (wealth, housing, education, healthy food and healthcare) for Black people. Recent studies point to implicit bias, and lack of cultural sensitivity playing a significant role in the health outcomes of Black cancer patients. For instance, despite NCCN guidelines, oncologists underprescribe chemotherapy for older Black women with ovarian cancer and underdose chemotherapy for Black women with cervical cancer. Moreover, Black women dying from advanced uterine cancer are given pain medication at lower rates &amp; there are disparities in palliative care utilization amongst Black patients with metastatic gynecologic cancer. The voices of Black patient advocates are frequently missing from research studies. By centering the voices of Black patient advocates, we can identify new means of addressing &amp; positively impacting disparities within the clinical care spectrum (from diagnosis to survivorship). Our study group, Black Voices on Gynecologic Cancer: Understanding Experiences, aimed to identify common and unique scenarios of racism and bias in the experiences of Black patients with gynecologic cancer seeking medical attention. Methods: Focus groups were advertised using social media and partner patient advocacy organizations. We conducted five focus groups of 24 Black gynecologic cancer survivors using a Zoom platform. Key themes were identified through individual and group review of transcripts. Results: The themes that emerged from the focus groups included: (1) lack of communication and/or clarity in patient/provider communication - “… my first appointment with my gyn I did…share that…I'm having these hot flashes, night sweats…so he gave me some medicine, but… they´d never really addressed and had a conversation about like this is what your body will be experiencing…So, I really have been dependent on other women that have gone through this.”, (2) insufficient mental health support throughout and after treatment, (3) experiences with misdiagnosis (4) provider’s inadequate management of patient pain, (5) failure to mention clinical trials and (6) difficulty navigating insurance. Conclusions: Our study identified gaps in the care of Black gynecologic cancer patients. The second phase of BVOGUE will reduce structural barriers that prohibit authentic patient and community engagement around gynecologic cancer care and participation in academic research for Black cancer patients. We will pilot modules for both cancer education and research advocacy. This model will serve as a roadmap for all cancer centers creating action plans for engagement, inclusion, and participation.